Camilo Garcia

Tumor Texture Analysis in 18F-FDG PET: Relationships Between Texture Parameters, Histogram Indices, Standardized Uptake Values, Metabolic Volumes, and Total Lesion Glycolysis

Texture indices are of growing interest for tumor characterization in 18F-FDG PET. Yet, on the basis of results published in the literature so far, it is unclear which indices should be used, what they represent, and how they relate to conventional indices such as standardized uptake values (SUVs), metabolic volume (MV), and total lesion glycolysis (TLG). We investigated in detail 31 texture indices, 5 first-order statistics (histogram indices) derived from the gray-level histogram of the tumor region, and their relationship with SUV, MV, and TLG in 3 different tumor types. Methods: Three patient groups corresponding to 3 cancer types at baseline were studied independently: patients with metastatic colorectal cancer (72 lesions), non–small cell lung cancer (24 lesions), and breast cancer (54 lesions). Thirty-one texture indices were studied in addition to SUVs, MV, and TLG, and 5 indices extracted from histogram analysis were also investigated. The relationships between indices were studied as well as the robustness of the various texture indices with respect to the parameters involved in the calculation method (sampling schemes and tumor volume of interest). Results: Regardless of the patient group, many indices were highly correlated (Pearson correlation coefficient |r| ≥ 0.80), making it desirable to focus on only a few uncorrelated indices. Three histogram indices were highly correlated with SUVs (|r| ≥ 0.84). Four texture indices were highly correlated with MV, and none was highly correlated with SUVs (|r| ≤ 0.55). The resampling formula used to calculate texture indices had a substantial impact, and resampling using at least 32 discrete values should be used for texture indices calculation. The texture indices change as a function of the segmentation method was higher than that of peak and maximum SUVs but less than mean SUV for 5 texture indices and was larger than that of MV for 14 texture indices and for the 5 histogram indices. All these results were extremely consistent across the 3 tumor types and explained many of the observations reported in the literature so far. Conclusion: None of the histogram indices and only 17 of 31 texture indices were robust with respect to the tumor-segmentation method. An appropriate resampling formula with at least 32 gray levels should be used to avoid introducing a misleading relationship between texture indices and SUV. Some texture indices are highly correlated or strongly correlate with MV whatever the tumor type. Such correlation should be accounted for when interpreting the usefulness of texture indices for tumor characterization, which might call for systematic multivariate analyses.

18F-FDG PET/CT for Early Prediction of Response to Neoadjuvant Lapatinib, Trastuzumab, and Their Combination in HER2-Positive Breast Cancer: Results from Neo-ALTTO

Molecular imaging receives increased attention for selecting patients who will benefit from targeted anticancer therapies. Neo-ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) enrolled 455 women with invasive human epidermal growth factor receptor 2 (HER2)–positive breast cancer and compared rates of pathologic complete response (pCR) to neoadjuvant lapatinib, trastuzumab, and their combination. Each anti-HER2 therapy was given alone for 6 wk, followed by 12 wk of the same therapy plus weekly paclitaxel. The early metabolic effects of the anti-HER2 therapies on the primary tumors and their predictive values for pCR were assessed in a subset of patients. Methods: Eighty-six patients underwent 18F-FDG PET/CT at baseline and weeks 2 and 6 of anti-HER2 treatment. An imaging core laboratory provided central validation, and 2 independent reviewers, masked to assigned treatment arm and clinical outcomes, performed consensus 18F-FDG PET/CT readings. Maximum standardized uptake value (SUVmax) reductions from baseline were used to measure metabolic response. Results: Seventy-seven of the 86 enrolled patients presented an evaluable baseline 18F-FDG PET/CT scan; of these, 68 and 66 were evaluable at weeks 2 and 6, respectively. Metabolic responses in the primary tumors were evident after 2 wk of targeted therapy and correlated highly with metabolic responses at week 6 (R2 = 0.81). pCRs were associated with greater SUVmax reductions at both time points. Mean SUVmax reductions for pCR and non-pCR, respectively, were 54.3% versus 32.8% at week 2 (P = 0.02) and 61.5% versus 34.1% at week 6 (P = 0.02). 18F-FDG PET/CT metabolic response rates at weeks 2 and 6 were 71.6% and 60%, respectively using European Organization for Research and Treatment of Cancer criteria; pCR rates were twice as high for 18F-FDG PET/CT responders than nonresponders (week 2: 42% vs. 21%, P = 0.12; week 6: 44% vs. 19%, P = 0.05). Conclusion: Early metabolic assessment using 18F-FDG PET/CT can identify patients with an increased likelihood of pCR after neoadjuvant trastuzumab, lapatinib, or their combination when given with chemotherapy.

Serial FDG–PET/CT for early outcome prediction in patients with metastatic colorectal cancer undergoing chemotherapy

BACKGROUNDnThe study purpose was to assess the predictive value of 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computerized tomography (CT) metabolic response after a single course of chemotherapy in patients with metastatic colorectal cancer (mCRC).nnnPATIENTS AND METHODSnFDG-PET/CT scans were carried out at baseline and on day 14 in 41 patients with unresectable mCRC treated with a biweekly regimen of chemotherapy. Metabolic nonresponse was defined by <15% decrease in FDG uptake in the dominant proportion of the patients lesions or if a lesion was found metabolically progressive. The PET-based response was correlated with radiological response (primary end point) and patients outcome (secondary end points).nnnRESULTSnRECIST response rate in metabolically responding patients was 43% (10 of 23) compared with 0% (0 of 17) in nonresponding patients (P=0.002). The metabolic assessments predictive performance for RECIST response was sensitivity 100% [95% confidence interval (CI) 69% to 100%], specificity 57% (95% CI 37% to 75%), positive predictive value 43% (95% CI 23% to 66%), and negative predictive value 100% (95% CI 80% to 100%). Comparing metabolically responding versus nonresponding patients, the hazard ratio (HR) was 0.28 (95% CI 0.10-0.76) for overall survival and 0.57 (95% CI 0.27-1.21) for progression-free survival.nnnCONCLUSIONnThe metabolic response measured by FDG-PET/CT after a single course of chemotherapy in mCRC is able to identify patients who will not benefit from the treatment.

A phase IIa, nonrandomized study of radium-223 dichloride in advanced breast cancer patients with bone-dominant disease

Radium-223 dichloride (radium-223) mimics calcium and emits high-energy, short-range alpha-particles resulting in an antitumor effect on bone metastases. This open-label, phase IIa nonrandomized study investigated safety and short-term efficacy of radium-223 in breast cancer patients with bone-dominant disease. Twenty-three advanced breast cancer patients with progressive bone-dominant disease, and no longer candidates for further endocrine therapy, were to receive radium-223 (50xa0kBq/kg IV) every 4xa0weeks for 4 cycles. The coprimary end points were change in urinary N-telopeptide of type 1 (uNTX-1) and serum bone alkaline phosphatase (bALP) after 16xa0weeks of treatment. Exploratory end points included sequential 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to assess metabolic changes in osteoblastic bone metastases. Safety data were collected for all patients. Radium-223 significantly reduced uNTX-1 and bALP from baseline to end of treatment. Median uNTX-1 change was −10.1xa0nmol bone collagen equivalents/mmol creatinine (−32.8xa0%; Pxa0=xa00.0124); median bALP change was −16.7xa0ng/mL (−42.0xa0%; Pxa0=xa00.0045). Twenty of twenty-three patients had FDG PET/CT identifying 155 hypermetabolic osteoblastic bone lesions at baseline: 50 lesions showed metabolic decrease (≥25xa0% reduction of maximum standardized uptake value from baseline) after 2 radium-223 injections [32.3xa0% metabolic response rate (mRR) at week 9], persisting after the treatment period (41.5xa0% mRR at week 17). Radium-223 was safe and well tolerated. Radium-223 targets areas of increased bone metabolism and shows biological activity in advanced breast cancer patients with bone-dominant disease.

Heterogeneity of Metabolic Response to Systemic Therapy in Metastatic Breast Cancer Patients

AIMnThe aim of this retrospective study was to describe the intra-individual heterogeneity of the ¹⁸F-labelled fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) response among lesions in bone-dominant metastatic breast cancer patients treated with systemic therapies.nnnPATIENTS AND METHODSnThe metabolic response was analysed by comparing PET/CT scans carried out before and during a new treatment phase (n=46) in 25 bone-dominant metastatic breast cancer patients. Patients presented both bone and extra-bone metastases in 48% treatment phases. The metabolic response was analysed according to European Organization for Research and Treatment of Cancer (EORTC) criteria. A heterogeneous response was defined as the coexistence of responding and non-responding lesions within the same patient.nnnRESULTSnThe lesion-based response analysis showed a heterogeneous metabolic response in 48% of treatment phases. In the subset with both bone and extra-bone metastases (n=20), PET/CT showed discordant responses between bone and extra-bone metastases in 6/20 (30%) treatment phases. Considering all the cases included in the study, the time to progression (TTP) was longer in cases with a metabolic response compared with the cases with a metabolic non-response (P=0.02). In cases with a PET/CT non-response, TTP seemed to be lower in those with a homogeneous non-response compared with those with a heterogeneous metabolic response (P=0.07).nnnCONCLUSIONnWhole-body FDG-PET allows frequent heterogeneous responses after systemic therapy to be identified in bone-dominant metastatic breast cancer patients.

Detection and Characterization of Tumor Changes in 18F-FDG PET Patient Monitoring Using Parametric Imaging

In PET-based patient monitoring, metabolic tumor changes occurring between PET scans are most often assessed visually or by measuring only a few parameters (tumor volume or uptake), neglecting most of the image content. We propose and evaluate a parametric imaging (PI) method to assess tumor changes at the voxel level. Methods: Seventy-eight pairs of tumor images obtained from baseline and follow-up 18F-FDG PET/CT for 28 patients with metastatic colorectal cancer were considered. For each pair, after CT-based registration of the PET volumes, the 2 PET datasets were subtracted. A biparametric graph of subtracted voxel values versus voxel values in the first PET scan was obtained. A model-based analysis of this graph was used to identify the tumor voxels in which significant changes occurred between the 2 scans and yielded indices characterizing these changes. The Response Evaluation Criteria in Solid Tumors (RECIST) based on the CT images obtained 5–8 wk after the second PET/CT scan were used to classify tumor masses as responding or progressive. On the basis of this classification, we compared the sensitivity and specificity of PI and an approach based on recommendations from the European Organization for Research and Treatment of Cancer (EORTC). Results: For tumor-based classification, the EORTC-based approach had a sensitivity and specificity of 85% and 52%, respectively, for detecting responding lesions, whereas PI had a sensitivity and specificity of 100% and 53%, respectively. None of responding tumors using RECIST was classified as progressive with the PI or EORTC-based criteria. Among the 14 progressive lesions according to RECIST, 12 were identified as progressive with PI whereas EORTC-based criteria classified only 1 as progressive and 13 as stable tumors. Considering the patient-based classification, none of the responders according to RECIST was classified as having progressive disease with the PI and EORTC-based criteria. PI has the advantage of showing a parametric image of the patient response to therapy, indicating potential heterogeneity in tumor response. Conclusion: The PI method has been successfully applied to characterize early metabolic tumor changes in 78 lesions from 18F-FDG PET/CT scans of patients with metastatic colorectal cancer during chemotherapy. The PI findings correlated well with the standard RECIST-based response assessment.

Comparison of PET metabolic indices for the early assessment of tumour response in metastatic colorectal cancer patients treated by polychemotherapy

PurposeTo compare the performance of eight metabolic indices for the early assessment of tumour response in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy.MethodsForty patients with advanced mCRC underwent two FDG PET/CT scans, at baseline and on day 14 after chemotherapy initiation. For each lesion, eight metabolic indices were calculated: four standardized uptake values (SUV) without correction for the partial volume effect (PVE), two SUV with correction for PVE, a metabolic volume (MV) and a total lesion glycolysis (TLG). The relative change in each index between the two scans was calculated for each lesion. Lesions were also classified as responding and nonresponding lesions using the Response Evaluation Criteria In Solid Tumours (RECIST) 1.0 measured by contrast-enhanced CT at baseline and 6–8xa0weeks after starting therapy. Bland-Altman analyses were performed to compare the various indices. Based on the RECIST classification, ROC analyses were used to determine how accurately the indices predicted lesion response to therapy later seen with RECIST.ResultsRECIST showed 27 responding and 74 nonresponding lesions. Bland-Altman analyses showed that the four SUV indices uncorrected for PVE could not be used interchangeably, nor could the two SUV corrected for PVE. The areas under the ROC curves (AUC) were not significantly different between the SUV indices not corrected for PVE. The mean SUV change in a lesion better predicted lesion response without than with PVE correction. The AUC was significantly higher for SUV uncorrected for PVE than for the MV, but change in MV provided some information regarding the lesion response to therapy (AUC >0.5).ConclusionIn these mCRC patients, all SUV uncorrected for PVE accurately predicted the tumour response on day 14 after starting therapy as assessed 4 to 6xa0weeks later (i.e. 6 to 8xa0weeks after therapy initiation) using the RECIST criteria. Neither correcting SUV for PVE nor measuring TLG improved the assessment of tumour response compared to SUV uncorrected for PVE. The change in MV was the least accurate index for predicting tumour response.

Progressive osteoblastic bone metastases in breast cancer negative on FDG-PET.

Positron emission tomography using F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is increasingly used in breast cancer. The new generation cameras integrate PET and CT within the same camera, allowing the simultaneous assessment of the structural and metabolic aspects of disease. There is presently a controversy on the clinical significance of osteoblastic bone metastases in breast cancer which are not detected on FDG-PET. It has been suggested that these radiologically dense lesions represent the result of successful treatment of initially osteolytic lesions. We report a case of a 65-year-old woman with a suspicion of recurrent breast cancer based on an increasing serum tumor marker. Serial PET/CT showed progressive blastic bone metastases on the CT without FDG uptake. These lesions were confirmed by bone single photon emission computed tomography. This case report shows: first, that progressive osteoblastic lesions can lack FDG-avidity, leading to a false-negative PET; and secondly, that bone scintigraphy should not be replaced by FDG-PET/CT for the detection of bone metastases in breast cancer.

Role of positron emission tomography in the management of head and neck cancer in the molecular therapy era.

Purpose of review The utility of positron emission tomography–computed tomography has increasingly been studied during the last years. Positron emission tomography–computed tomography offers a holistic approach of cancer diagnosis as it can integrate structural, functional, metabolic, and molecular information of tumour. The technique offers three-dimensional, high-resolution, whole body, and quantitative imaging. 18F-Fluoro-2-deoxy-D-glucose still remains the only tracer widely available. Other tracers have been designed for assessment of proliferation, amino acid uptake, and hypoxia. Recent findings 18F-Fluoro-2-deoxy-D-glucose positron emission tomography–computed tomography seems the most appropriate technique for the assessment of locoregional lymph node involvement in head and neck cancer. False negativity of positron emission tomography–computed tomography in case of micrometastatic lymph node disease should be compensated by the implementation of the sentinel node scintigraphy guided biopsy. 18F-Fluoro-2-deoxy-D-glucose positron emission tomography–computed tomography has a very high sensitivity and negative predictive value in detecting residual disease after radiotherapy or early recurrent disease. Radiotherapy planning can use the 18F-fluoro-2-deoxy-D-glucose uptake distribution for increasing the accuracy of delineation of the target volumes in conformal radiotherapy. Positron emission tomography–computed tomography with other tracers such as deoxy-18F-fluorothymidine for proliferation mapping and [F-18] fluoromisonidazole for hypoxia mapping are currently being studied. Summary Major studies have now confirmed the utility of positron emission tomography–computed tomography in the different phases of diagnostic and therapeutic phases of the management of patients with head and neck cancer.

Lesion-based detection of early chemosensitivity using serial static FDG PET/CT in metastatic colorectal cancer

PurposeMedical oncology needs early identification of patients that are not responding to systemic therapy. 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) performed before and early during treatment has been proposed for this purpose. However, the best way to assess the change in FDG uptake between two scans has not been identified. We studied cutoff thresholds to identify responding tumours as a function of the method used to measure tumour uptake.MethodsThe study included 28 metastatic colorectal cancer (mCRC) patients who underwent 2 FDG PET/CT scans (baseline and at day 14 of the first course of polychemotherapy). For 78 tumour lesions, 4 standardized uptake value (SUV) indices were measured: maximum SUV (SUVmax) and mean SUV in a region obtained using an isocontour (SUV40xa0%), with each of these SUV normalized either by the patient body weight (BW) or body surface area (BSA). The per cent change and absolute change in tumour uptake between the baseline and the early PET scans were measured based on these four indices. These changes were correlated to the RECIST 1.0-based response using contrast-enhanced CT at baseline and at 6–8xa0weeks on treatment.ResultsThe 78 tumours were classified as non-responding (NRL, nu2009=u200958) and responding lesions (RL, nu2009=u200920). Receiver-operating characteristic (ROC) curves characterizing the performance in NRL/RL classification using early FDG PET uptake had areas under the curve between 0.75 and 0.84, without significant difference between the indices. The cutoff threshold in FDG uptake per cent change to get a 95xa0% sensitivity of RL detection depended on the way uptake was measured: −14xa0% (specificity of 53xa0%) and −22xa0% (specificity of 64xa0%) for SUVmax and SUV40xa0%, respectively. Thresholds expressed as absolute SUV decrease instead of per cent change were less sensitive to the SUV definition: an SUV decline by 1.2 yielded a sensitivity of RL detection of 95xa0% for SUVmax and SUV40xa0%. For a given cutoff threshold, the sensitivity was the same whatever the normalization (by BSA or BW).ConclusionA 14xa0% drop of tumour FDG SUVmax, 22xa0% drop of SUV40xa0% or 1.2 drop of SUVmax or SUVmean after one single course of polychemotherapy predicts objective response in mCRC lesions with a high sensitivity, potentially allowing the early identification of non-responding patients.